title: Quinazolinecarboline alkaloid evodiamine as scaffold for targeting topoisomerase I and sirtuins.
abstract: This paper reports the synthesis of a series of evodiamine derivatives. We assayed the ability to inhibit cell growth on three human tumour cell lines (H460, MCF-7 and HepG2) and we evaluated the capacity to interfere with the catalytic activity of topoisomerase I both by the relaxation assay and the occurrence of the cleavable complex. Moreover, whose effect on sirtuins 1, 2 and 3 was investigated. Finally, molecular docking analyses were performed in an attempt to rationalize the biological results.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Christodoulou
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sacchetti
authors.forename: Valentina
authors.initials: V
authors.lastname: Ronchetti
authors.forename: Stefania
authors.initials: S
authors.lastname: Caufin
authors.forename: Alessandra
authors.initials: A
authors.lastname: Silvani
authors.forename: Giordano
authors.initials: G
authors.lastname: Lesma
authors.forename: Gabriele
authors.initials: G
authors.lastname: Fontana
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Minicone
authors.forename: Benedetta
authors.initials: B
authors.lastname: Riva
authors.forename: Micol
authors.initials: M
authors.lastname: Ventura
authors.forename: Maija
authors.initials: M
authors.lastname: Lahtela-Kakkonen
authors.forename: Elina
authors.initials: E
authors.lastname: Jarho
authors.forename: Valentina
authors.initials: V
authors.lastname: Zuco
authors.forename: Franco
authors.initials: F
authors.lastname: Zunino
authors.forename: Nadine
authors.initials: N
authors.lastname: Martinet
authors.forename: Federico
authors.initials: F
authors.lastname: Dapiaggi
authors.forename: Stefano
authors.initials: S
authors.lastname: Pieraccini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sironi
authors.forename: Lisa
authors.initials: L
authors.lastname: Dalla Via
authors.forename: Ornella Maria
authors.initials: OM
authors.lastname: Gia
authors.forename: Daniele
authors.initials: D
authors.lastname: Passarella
mesh_terms: D000470:Alkaloids / Q000737:chemistry; D001665:Binding Sites; D002243:Carbolines / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D002243:Carbolines; D011799:Quinazolines; D059004:Topoisomerase I Inhibitors; C049639:evodiamine; D037761:Sirtuins; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human
keywords: Evodiamine; Quinazolinecarboline alkaloids; Sirtuins; Topoisomerase I; enantiomer; ent; epi; epimer